scholarly journals Phenotype molding of T cells in colorectal cancer by single‐cell analysis

2020 ◽  
Vol 146 (8) ◽  
pp. 2281-2295 ◽  
Author(s):  
Jiabo Di ◽  
Maoxing Liu ◽  
Yingcong Fan ◽  
Pin Gao ◽  
Zaozao Wang ◽  
...  
2021 ◽  
Vol 8 (8) ◽  
pp. 2004320
Author(s):  
Hua Wang ◽  
Peng Gong ◽  
Tong Chen ◽  
Shan Gao ◽  
Zhenfeng Wu ◽  
...  

2021 ◽  
Author(s):  
Ke-Yue Ma ◽  
Alexandra A. Schonnesen ◽  
Chenfeng He ◽  
Amanda Y. Xia ◽  
Eric Sun ◽  
...  

2018 ◽  
Vol 102 ◽  
pp. S139
Author(s):  
Nynke Kannegieter ◽  
Dennis Hesselink ◽  
Marjolein Dieterich ◽  
Gretchen de Graav ◽  
Rens Kraaijeveld ◽  
...  

1999 ◽  
Vol 194 (2) ◽  
pp. 150-161 ◽  
Author(s):  
Lisa L. Salazar Murphy ◽  
Melissa M. Mazanet ◽  
Angela C. Taylor ◽  
Javier Mestas ◽  
Christopher C.W. Hughes

2021 ◽  
Author(s):  
Xanthi Stachtea ◽  
Maurice B. Loughrey ◽  
Manuela Salvucci ◽  
Andreas U. Lindner ◽  
Sanghee Cho ◽  
...  

AbstractColorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as ‘high’, ‘moderate’ or ‘low’, for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1−) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1− Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1− Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1−. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Trine Sundebo Meldgaard ◽  
Fabiola Blengio ◽  
Denise Maffione ◽  
Chiara Sammicheli ◽  
Simona Tavarini ◽  
...  

CD8+ T cells play a key role in mediating protective immunity after immune challenges such as infection or vaccination. Several subsets of differentiated CD8+ T cells have been identified, however, a deeper understanding of the molecular mechanism that underlies T-cell differentiation is lacking. Conventional approaches to the study of immune responses are typically limited to the analysis of bulk groups of cells that mask the cells’ heterogeneity (RNA-seq, microarray) and to the assessment of a relatively limited number of biomarkers that can be evaluated simultaneously at the population level (flow and mass cytometry). Single-cell analysis, on the other hand, represents a possible alternative that enables a deeper characterization of the underlying cellular heterogeneity. In this study, a murine model was used to characterize immunodominant hemagglutinin (HA533-541)-specific CD8+ T-cell responses to nucleic- and protein-based influenza vaccine candidates, using single-cell sorting followed by transcriptomic analysis. Investigation of single-cell gene expression profiles enabled the discovery of unique subsets of CD8+ T cells that co-expressed cytotoxic genes after vaccination. Moreover, this method enabled the characterization of antigen specific CD8+ T cells that were previously undetected. Single-cell transcriptome profiling has the potential to allow for qualitative discrimination of cells, which could lead to novel insights on biological pathways involved in cellular responses. This approach could be further validated and allow for more informed decision making in preclinical and clinical settings.


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